Abstract
Purpose
To report a case of recurrent iris post-transplant lymphoproliferative disorder (PTLD) treated with ultra-low-dose (boom-boom) radiotherapy (RT).
Observations
A 12-year-old Caucasian male with a history of bilateral, recurrent iris PTLD of the extranodal marginal zone lymphoma (MALT) type presented with persistent bilateral anterior chamber cellular infiltration, which was incompletely controlled on topical corticosteroids, and with elevated intraocular pressure (IOP) in the right eye secondary to steroid response. The patient was diagnosed with PTLD recurrence and was successfully treated with ultra-low-dose RT to both eyes in 2 fractions of 2 Gy. At 15 month follow-up the patient maintained complete disease control with normal IOP off all topical ophthalmic medications.
Conclusions and Importance
Ultra-low-dose RT for ocular PTLD of the MALT subtype represents a novel therapeutic approach that may provide a durable treatment response and could be considered as either primary or adjuvant therapy for this rare condition.
1
Introduction
Post-transplant lymphoproliferative disorders (PTLDs) are common among solid and hematopoietic transplant recipients and may affect both pediatric and adult patients. Ocular PTLD is quite uncommon with a limited number of cases described in the literature. The optimal therapy for this disorder has not been established due to the rarity of this condition, but typically it has been treated with systemic rituximab alone or in combination with low-dose chemotherapy. We previously reported the use of systemic rituximab combined with intraocular rituximab and methotrexate. In this report, we provide follow-up of the same case treated with ultra-low dose (boom-boom) radiotherapy (RT) for recurrent PTLD.
1.1
Case presentation
A 12-year-old boy presented for persistent bilateral anterior chamber cellular infiltration in the setting of previously treated iris PTLD. Historical details of the case can be found in the prior report on this patient. In brief, he underwent orthotopic heart transplantation and developed chronic low-grade Epstein-Barr virus (EBV) viremia due to EBV seromismatch. Five years later, he presented with bilateral granulomatous anterior chamber cellular reaction and multiple iris nodules. The patient underwent systemic screening with routine blood work (complete blood cell count, liver enzymes, and electrolytes), brain magnetic resonance imaging, whole-body positron emission tomography, and cerebrospinal fluid analysis, which revealed no systemic lymphoproliferative process. Iris biopsy revealed CD20-positive B-cells intermixed with plasma cells resembling extranodal marginal zone lymphoma (MALT). A diagnosis of iris PTLD with MALT-like features was made, with no associated systemic lymphoproliferative process. Following no improvement with topical 1% prednisolone acetate and cessation of mycophenolate mofetil immunosuppression, he was managed with concomitant systemic rituximab and a total of 5 bilateral intraocular rituximab injections (1 mg/0.1 mL) administered under general anesthesia, with initial disease control. A few months later, recurrence of anterior chamber cellular infiltration and keratic precipitates prompted a single bilateral intravitreal methotrexate (400 mcg in 0.1 mL) injection under general anesthesia. This led to sustained remisson with control of cellular infiltration for 4 months. Subsequent follow-up 4 months later showed no evidence of ocular toxicity from methotrexate. However, worsening recurrent cellular infiltration in the interim prompted initiation of topical 1% prednisolone acetate 3–4 times daily and disease progression 11 months after methotrexate injection prompted increase of topical corticosteroids to 6 times daily, with worsening cellular infiltration on several attempts to wean topical therapy. This prompted re-referral of the patient to our ocular oncology service.
The patient was examined 28 months after methotrexate injection with visual acuity of 20/30 and 20/25 and intraocular pressure (IOP) of 32 and 10 mmHg in the right and left eyes, respectively. Anterior chamber examination revealed 1+ and trace cellular infiltration in the right and left eyes, respectively. There were several small keratic precipitates in the right eye and none in the left eye. The 1% prednisolone acetate was tapered and a topical ocular hypotensive agent was initiated in the right eye, while maintaining 1% prednisolone acetate three times daily in the left eye. The patient was examined 1 month later, and IOP had improved to 11 mmHg in the right eye, although there was persistent anterior chamber infiltration and keratic precipitates. The decision was made to proceed with ultra-low-dose “boom boom” RT using a total of 4 Gray (Gy) delivered in 2 fractions of 2 Gy on consecutive days, with the intention to render a curative treatment and enable cessation of topical corticosteroids.
A single anterior proton beam was used to treat each anterior chamber and iris accounting for 3 mm setup and treatment uncertainties ( Fig. 1 A). To reduce radiation scatter to periocular adnexa, orbital rim bones, and midfacial soft tissues the proton beam was delivered through a bolus shell of 42 mm water-equivalent thickness placed 3 cm from the patient’s surface ( Fig. 1 B). Each of the two treatments was performed under general anesthesia, and ocular alignment was verified by computed tomography-on-rails in the proton treatment room. One month following RT, the patient had neither anterior chamber cellular infiltration nor keratic precipitates. Visual acuity improved to 20/20 in the right eye and was stable at 20/25 in the left eye; IOP was 7 and 10 mmHg in the right and left eyes, respectively. With continued follow-up over several months, topical corticosteroid was gradually tapered and IOP lowering drops were discontinued.
